Hydrochloric Acid → 2-Isopropoxycarbonylamino-6-methyl-benzoic acid methyl ester

HRID 2353942Notes

Reaction equation

HRID 2353942 reaction equation
Cl[C:2]([O:4][CH:5]([CH3:7])[CH3:6])=[O:3].[CH3:8][O:9][C:10](=[O:19])[C:11]1[C:16]([CH3:17])=[CH:15][CH:14]=[CH:13][C:12]=1[NH2:18].N1C=CC=CC=1.Cl>ClCCl>[CH3:8][O:9][C:10](=[O:19])[C:11]1[C:16]([CH3:17])=[CH:15][CH:14]=[CH:13][C:12]=1[NH:18][C:2]([O:4][CH:5]([CH3:7])[CH3:6])=[O:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 7917Isopropyl chloroformateHCID 583916Benzoic acid, 2-amino-6-methyl-, methyl ester

Product 1

HCID 590031022-Isopropoxycarbonylamino-6-methyl-benzoic acid methyl esterYield 76.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add isopropyl chloroformate (19.8 mL, 19.8 mmol, 1.0 M in toluene) dropwise to a solution of 2-Amino-6-methyl-benzoic acid methyl ester (3.27 g, 19.8 mmol) and pyridine (4.0 mL, 50 mmol) in dichloromethane (39 mL) at 0° C. under an atmosphere of nitrogen and stir at room temperature for 14 h. Add 1M HCl and separate the layers. Extract the aqueous layer with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (3.80 g, 76%): 1H NMR (CDCl3) δ 1.29 (d, J=6.5 Hz, 6H), 2.43 (s, 3H), 3.94 (s, 3H), 5.00 (septuplet, J=6.5 Hz, 1H), 6.90 (d, J=8.1 Hz, 1H), 7.32 (t, J=8.1 Hz, 1H), 8.07 (d, J=8.1 Hz, 1H), 8.86 (brs, 1H). MS (ES+): 252 (M+H).

Workup

  1. customseparate the layers
  2. extractionExtract the aqueous layer with dichloromethane
  3. dry with materialDry the organic layer over anhydrous sodium sulfate
  4. filtrationfilter
  5. customremove the solvent under reduced pressure
  6. customPurify the residue by flash chromatography
  7. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-3405d41bf48c4c1fa54493c22525018e
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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